Antisense oligonucleotides that inhibit expression of human replication-initiation protein as well as methods of preventing or treating hyperproliferative conditions using said oligonucleotides are disclosed. One aspect provides an antisense oligonucleotides that inhibits the expression of human replication-initiation protein and has a sequence complementary to at least a portion of a target sequence encoding a human replication-initiation gene. By administering a therapeutically effective amount of antisense oligonucleotides or by contacting the hyperproliferating cells with an effective amount of antisense oligonucleotides, expression of replication-initiation protein is inhibited. Methods of screening and testing active antisense oligonucleotides for their ability to inhibit gene expression are also disclosed.